Disruption of Ephrin B/Eph B Interaction Results in Abnormal Cochlear Innervation Patterns
Disruption of Ephrin B/Eph B Interaction Results in Abnormal Cochlear Innervation Patterns
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DOI：
10.1002/lary.21861
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发表时间：
2011-07-01
期刊：
影响因子：
2.6
通讯作者：
Lee, Kenneth H.
中科院分区：
文献类型：
--
作者：
Zhou, Constance Q.;Lee, James;Lee, Kenneth H.
目的：为了确定B ephrin和Eph在耳蜗中的表达模式，并确定ephrin B/Eph B相互作用的破坏在两个培养的螺旋神经节神经元和活的animals.Study Design的耳蜗的功能后果：各种B ephrin和Eph的表达模式进行了测定在小鼠Lac-Z突变。单个B ephrin和Eph蛋白的无效功能的小鼠和那些与多个敲除的耳蜗神经支配patterns.Methods：小鼠与B ephrin和Eph破坏的if-半乳糖苷酶基因在P6处死，和他们的耳蜗分离和处理Lac-Z染色，以确定这些蛋白在耳蜗组织中的表达。螺旋神经节细胞从野生型以及ephrin B1基因敲除小鼠分离和共培养Eph B2表达Cos 1细胞和轴突长度进行了测定。荧光亲脂染料标记螺旋神经节细胞神经纤维，以确定耳蜗神经支配模式在野生型和基因敲除mice.Results：Eph B1，B2，和ephrin B2，但没有B3表达在耳蜗。Eph B2抑制野生型小鼠螺旋神经节细胞轴突的生长，但不能抑制培养中ephrin B1敲除小鼠的生长。敲除小鼠与空功能的ephrin B1单独或Eph B1，Eph B2，Eph B3的组合表现出异常的神经支配模式在Corti.Conclusions的器官：中断的B ephrin和Ephs的结果在螺旋神经节细胞的功能后果，这表明这些蛋白质发挥了作用，在建立正常的神经支配模式在耳蜗。
Objective: To determine the expression patterns of B ephrins and Ephs in the cochlea and identify functional consequences of disruption of ephrin B/Eph B interactions in both cultured spiral ganglion neurons and in the cochlea of live animals.Study Design: The expression patterns of various B ephrins and Ephs were determined in mice with Lac-Z mutation. Mice with null function of individual B ephrin and Eph proteins and those with multiple knockouts were studied for cochlear innervation patterns.Methods: Mice with B ephrins and Ephs disrupted with the if-galactosidase gene were sacrificed at P6, and their cochleae isolated and processed for Lac-Z staining to determine expression of these proteins in cochlear tissue. Spiral ganglion cells from wild-type as well as ephrin B1 knockout mice were isolated and cocultured with Eph B2 expressing Cos1 cells and neurite lengths were determined. Fluorescent lipophillic dyes were used to label spiral ganglion cell nerve fibers to determine cochlear innervation patterns in wild-type and knockout mice.Results: Eph B1, B2, and ephrin B2 but not B3 was expressed in the cochlea. Eph B2 inhibited outgrowth of spiral ganglion cell axons from wild-type mice, but not from ephrin B1 knockout mice in culture. Knockout mice with null function of ephrin B1 alone or Eph B1, Eph B2, Eph B3 in combination demonstrated abnormal innervation patterns in the organ of Corti.Conclusions: Disruption of B ephrins and Ephs results in functional consequences in spiral ganglion cells, suggesting that these proteins play a role in establishing normal innervation patterns in the cochlea.